Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis.

Cell Death & Disease
Shuoyi JiangXinliang Mao

Abstract

Chronic myelogenous leukemia (CML) is a clonal malignancy of hematopoietic stem cells featured with the fusion protein kinase BCR-ABL. To elicit the mechanism underlying BCR-ABL stability, we perform a screen against a panel of deubiquitinating enzymes (DUBs) and find that the ubiquitin-specific protease 7 (USP7) drastically stabilizes the BCR-ABL fusion protein. Further studies show that USP7 interacts with BCR-ABL and blocks its polyubiquitination and degradation. Moreover, USP7 knockdown triggers BCR-ABL degradation and suppresses its downstream signaling transduction. In line with this finding, genetic or chemical inhibition of USP7 leads to BCR-ABL protein degradation, suppresses BCR/ABL signaling, and induces CML cell apoptosis. Furthermore, we find the antimalarial artesunate (ART) significantly inhibits USP7/BCR-ABL interaction, thereby promoting BCR-ABL degradation and inducing CML cell death. This study thus identifies USP7 as a putative Dub of BCR-ABL and provides a rationale in targeting USP7/BCR-ABL for the treatment of CML.

References

Jul 15, 1999·The New England Journal of Medicine·S FaderlH M Kantarjian
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·N KashigeR Kobayashi
Aug 27, 2005·Clinical Pharmacokinetics·Bin PengHorst Schran
Sep 12, 2006·Nature Cell Biology·Armando van der HorstBoudewijn M T Burgering
Dec 14, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniela Cilloni, Giuseppe Saglio
Dec 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xianping ShiJinbao Liu
Dec 3, 2014·The International Journal of Biochemistry & Cell Biology·Guodong ChenXinliang Mao
Jan 28, 2017·Scientific Reports·Huilin HuangLianghu Qu
Nov 23, 2017·Journal of the National Cancer Institute·Rebecca MitchellG Vignir Helgason
Jun 15, 2019·Acta Pharmacologica Sinica·Xue-Han ChenTie Zhang
Dec 12, 2019·The Journal of Biological Chemistry·Yuanming HeXinliang Mao

❮ Previous
Next ❯

Citations

Aug 30, 2021·Biomarker Research·Hu LeiYingli Wu
Oct 23, 2021·Biochemical Pharmacology·Mathilde MullardFranck Verrecchia

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis